Wnt5a signaling in Malignant Melanoma
Author
Summary, in English
In this thesis, we investigate different processes downstream of Wnt5a that can lead to increased aggressiveness of malignant melanoma. Our studies show that the secreted Wnt modulator, SFRP3 is down-regulated in malignant melanoma patients. Using melanocyte and malignant melanoma cell lines, we demonstrate that the down-regulation is due to methylation. Functional studies show that SFRP3 can inhibit Wnt5a signaling and induce a decrease in migration and invasion. Furthermore, by analyzing the effects of Wnt5a on the malignant melanoma proteome, we provide evidence for a cell context dependent reprogramming of cellular metabolism induced by Wnt5a. Activation of Wnt5a signaling in melanoma cell lines resulted in a pro-tumorigenic effect by favoring aerobic glycolysis. Finally, we investigate the relationship between Wnt5a and secreted pro-tumorigenic factors. We found that Wnt5a could activate regulated secretion of IL-6 and VEGF, dependent on cytoskeletal re-arrangements mediated via calcium signaling and Cdc42 activation.
Taken together these data suggests that, in melanoma, an altered Wnt5a signal can induce different pro-tumorigenic effects. This thesis highlights the complexity of Wnt signaling in general and Wnt5a signaling in melanoma in particular and extends our knowledge of the mechanisms behind progression of malignant melanoma.
Department/s
- Experimental Pathology, Malmö
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publishing year
2011
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2011:104
Full text
Document type
Dissertation
Publisher
Department of Laboratory Medicine, Lund University
Topic
- Cancer and Oncology
Status
Published
Research group
- Experimental Pathology, Malmö
Supervisor
- Tommy Andersson
- Karin Leandersson
- Victoria Sherwood
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-86871-54-3
Defence date
16 December 2011
Defence time
13:00
Defence place
Auditorium, CRC, Entrance 72, Skåne University Hospital, Malmö
Opponent
- Gunnar Schulte